Cause Of Autoimmune Hemolytic Anemia Research Articles

Neutrophilic erythrophagocytosis in a child with paroxysmal cold hamoglobinuria.

A 3-year-old previously healthy male child presented to the emergency department with a 2-day history of fatigue, jaundice, and dark-brown colored urine following a week of vomiting and fever. There was no significant past medical, drug or family history. Clinical examination was normal apart from jaundice and mildly enlarged spleen on physical examination, confirmed on ultrasonography. Blood tests revealed hemoglobin of 57 g/L, haptoglobin of <0.2 g/L bilirubin of 80 μmol/L, lactate dehydrogenase of 1902 U/L, and C-reactive peptide of 126 mg/L. Direct antiglobulin test was strongly positive for C3d only. Donath–Landsteiner (D-L) antibody positivity was not demonstrated. Urine examination revealed hemoglobinuria. Viral swabs were negative for COVID-19, respiratory syncytial virus (RSV), influenza A&B, and serology did not demonstrate recent infection by cytomegalovirus, Epstein–Barr virus, or parvovirus B19. Blood cultures were negative. These results were consistent with auto-immune hemolytic anemia of intravascular type. His peripheral blood smear (shown in the panel) revealed features of hemolytic anemia with polychromasia, red cell agglutination, and spherocytosis. In addition to this, neutrophilic erythrophagocytosis (Figure 1, blue arrows) can be seen, which is typical in paroxysmal cold hemoglobinuria (PCH), though it can occasionally be seen in other conditions such as myelodysplasia [1]. A diagnosis of PCH was reached and patient was treated according to the standard protocols with warmed blood transfusions and folic acid. He required multiple transfusions during the first 2 weeks of presentation. He was discharged from the hospital once his hemoglobin stabilized. We continued to monitor his condition as an outpatient for few weeks and his hemoglobin showed a consistent upward trend, completely resolving within 2 weeks of discharge. Although PCH is a rare disorder, it is one of the most common causes of autoimmune hemolytic anemia in children [2]. Historically, it was often associated with chronic Syphilis infection and patients would experience paroxysms of hemolysis on exposure to cold; however, nowadays, it almost always occurs as acute transient anemia in children after some form of viral illness. As a result, bouts of hemolysis on exposure to cold are now rarely demonstrated [2]. Symptoms are normally transient and require no specific treatment other than supportive measures like transfusion support. Immunosuppression with steroids has not proven to be effective [2]. PCH is classically diagnosed following demonstration of a D-L antibody. This specialized test is performed in reference laboratories in the United Kingdom. The D-L antibody is a biphasic, usually IgG antibody, that binds with the “P” antigen on red cells at low temperature and causes complement-mediated lysis in red cells coated with C3 on rewarming [3]. Difficulty in maintaining the correct temperature during sample collection and handling will lead to a falsely negative result [3], and it is the most likely reason for this result in this case. A negative D-L antibody test should not dissuade the clinician from a diagnosis of PCH when the clinical features and other tests are otherwise supportive. The authors declare they have no conflicts of interest. The authors received no specific funding for this work. Written consent was obtained from the patient's guardian. Data are available upon reasonable request from the corresponding author.

Steroid Response in Autoimmune Hemolytic Anemia

Background: Auto-immune hemolytic anemia is an uncommon but not rare disorder. Steroid is the best and commonly used drug for this disorder because it is cheap, easily available and less toxic. But there are a few studies on evaluation of response of steroids in auto-immune hemolytic anemia in our country. Objectives: The purpose of the study was to find out the mean duration for attaining response with prednisolone at the dose of 1 mg/kg body weight, to categorize the patients according to response criteria and to find out the adverse effects due to prednisolone. Methodology: This was a longitudinal and prospective study done in Hematology department of Dhaka Medical College Hospital, Dhaka over a period of one and half year from January 2011 to July 2012. All diagnosed cases of auto-immune hemolytic anemia attending in the hematology department full filling the inclusion and exclusion criteria were included in the study. Data were collected by using a structured questionnaire after taking written consent and history and doing physical examination and relevant baseline investigations. Patients were followed up for two weeks and further physical examination and investigations were done during this time. Result: Mean age of the patient was 33.08 year. Most of the patients (33.33%) belonged to &lt;20 year age group. Progressive pallor, weakness and anemia were the most prominent clinical features (100%), followed by jaundice (50%), splenomegaly (50%), dyspnea (45.8%), hepatosplenomegaly (33.33%), palpable lymph nodes (8.33%) purpuric spot (2%), bleeding manifestation (2%) and bloody diarrhea (2%). No cause of autoimmune hemolytic anemia was found in 43 (89.5%) patients. Among 5 patients with autoimmune hemolytic anemia 3 (6.25%) had non-Hodgkin’s lymphoma, 1 (2.08%) had chronic lymphocytic leukemia and 1 (2.08%) had ulcerative colitis. DAT (Direct antiglobulin test) was found positive in 36 patients (75%) and both DAT and indirect antiglobulin test were found positive in 12 patients (25%). Out of 48 patients 32 patients (66.66%) responded within one week and the rest 16 patients (33.34%) responded within two weeks of starting treatment. 43 patients (89.58%) showed complete response and the rest 5 patients (10.42%) showed partial response. Conclusion: Most of the patients responded completely within one week and no patients were found without response. So, Steroid (prednisolone) is very cheap and effective drug for the vast poor people of Bangladesh. J Shaheed Suhrawardy Med Coll 2021; 13(1): 41-45

RECURRENT AUTOIMMUNE HEMOLYTIC ANEMIA AFTER MRNA COVID-19 VACCINE (PFIZER-BIONTECH)

Case reportOne of the causes of autoimmune hemolytic anemia is drugs. Vaccination is the most important step in the management of the COVID-19 pandemic. After receiving the m-RNA COVID-19 (Pfizer-BioNTech) vaccine, the patient admitted with weakness and jaundice for the last three days. Laboratory results are consistent with AIHA recurrence. Splenectomy was performed after the patient stabilized with rituximab therapy. Especially newly developed therapeutic agents have a potential risk of new side effects.

S2796 Warm Autoimmune Hemolytic Anemia Secondary to Acute Hepatitis B Virus Infection

Introduction: Autoimmune hemolytic anemia (AIHA) is a rare extrahepatic manifestation, typically associated with HIV, hepatitis C, E, and Epstein Barr virus (EBV) infections. Hepatitis B virus (HBV) induced AIHA is an unusual association, not previously described in the literature. We report the first case of HBV-induced warm-AIHA, successfully treated with corticosteroids and anti-viral therapy. Case Description/Methods: A 67-year-old man presented to our hospital with one month of myalgias, arthralgias, and fatigue. He had no known history of the lymphoproliferative disorder, autoimmune disease, immunodeficiency, malignancy, or alcohol abuse. He lived in the woods and reported previous tick exposure and recent unprotected sexual encounters with multiple intravenous drug users. His physical examination revealed mild scleral icterus. Laboratory workup was notable for hemoglobin (Hb) 12.5 gm/dL, reticulocyte count 4.1%, elevated aspartate aminotransferase 493 units/L, alanine aminotransferase 693 units/L, total bilirubin 5.3mg/dL with indirect bilirubinemia 2.4 mg/dL, lactate dehydrogenase 1,158 units/L, and undetectable haptoglobin. Immunohematologic studies showed a direct antiglobulin test positive for IgG and C3 with isolation of warm autoantibodies by elution, consistent with a diagnosis of warm AIHA. Workup to elucidate the cause of AIHA including ANA, anti-proteinase-3, myeloperoxidase antibodies, peripheral blood smear, malaria smear, northeast tick panel, serum protein electrophoresis, and immunofixation were unrevealing. HIV, hepatitis A, C, E, and EBV infections were ruled out. HBV serologies revealed positive HBs-antigen, anti-HBc IgM, and PCR quantification HBV DNA 824,000,000 IU/ml, consistent with acute HBV infection. A diagnosis of warm AIHA secondary to acute HBV infection was made. 1mg/kg/day of prednisone and Tenofovir 25 mg/day were started. During the hospitalization, his anemia worsened, reaching a Hb nadir of 5.2 gm/dl and requiring ten units of packed red blood cell transfusions. He eventually stabilized at day 18, followed by a sustained virological response, clinical and laboratory remission of AIHA. Discussion: This case highlights AIHA as an unusual manifestation of acute HBV infection. An association between AIHA and hepatic viruses, including HIV, HCV, and EBV, has been well recognized. Acute HBV infection induced AIHA has not been reported in the literature yet. Therefore, clinicians should consider HBV infection in any patient presenting with new-onset AIHA of unclear etiology.Figure 1.: The patient's jaundice on physical exam.

WARM AGGLUTIN AUTOIMMUNE HEMOLYTIC ANEMIA ASSOCIATED WITH EPSTEIN BARR VIRUS

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Autoimmune hemolytic anemia (AIHA) is a relatively rare disorder (1-3 per 100 000) characterized by antibody production against autologous erythrocytes [1]. We present a novel case of warm agglutinin, autoimmune hemolytic anemia associated with Epstein-Barr Virus (EBV). CASE PRESENTATION: A 79-year-old woman with hypothyroidism was referred from the outpatient clinic after labs showed hemoglobin (Hgb) of 6.7 mg/dL. She complained of fatigue and dyspnea for 5 days. She had yellowing of skin and dark urine for 2 days. Vitals showed a blood pressure of 87/27 mmHg with a heart rate of 87 bpm. Repeat Hgb was 4.7 g/dL associated with mean corpuscular volume 111.6 fL. White cell count was elevated at 18. Leukocyte Alkaline Phosphatase score was elevated at 50. Direct Coombs test was positive with IgG and anti-C3 with warm agglutins. Haptoglobin was <10mg/dL, Lactate dehydrogenase 900U/L, and ferritin 1747. She received 3 units of packed red blood cells (RBC) and was started on corticosteroids. Peripheral blood smear showed left shift with increased bands, and megaloblastic granulocytes. Serum B12 level was 63ng/mL (N >200). Intrinsic factor was within normal limits. Ebstein Barr Virus IgG titers were elevated at 50 times limit upper limit of normal. All other tests for infectious causes of AIHA were negative. She was not on any medications known to cause AIHA. The patient reported resolution of symptoms by admission day 2. Hgb improved to baseline at 9.4 mg/dL and repeat MCV was 94.8 fL. The patient was subsequently discharged with B12 supplementation and continued to be symptom-free 4 weeks later. DISCUSSION: AIHA has a broad differential, with etiologies including medications, viruses, and hematological malignancies. EBV has a well-established connection with cold agglutin AIHA. IgM antibodies formed against EBV can cross-react against erythrocytes, reacting at 1-3 degrees Celsius, hence classified as cold agglutinin hemolytic anemia. However, it is not known if EBV can also induce warm agglutination. An extensive literature review returned a single report of fatal AIHA due to IgG warm agglutination exacerbated by EBV [2]. AIHA may have also be exacerbated by irregular erythropoiesis. Megaloblastic erythrocytes may have unique membrane antigens that present easier targets for circulating antibodies, thus driving hemolysis [3].Macrocytosis was likely due to B12 deficiency in this case, however other autoimmune diseases like pernicious anemia may be associated with AIHA, and warrant investigation. LAP score was also done to differentiate between reactive leukocytosis vs hematological malignancies such as chronic myelogenous leukemia, which also causes AIHA. CONCLUSIONS: EBV is classically associated with cold agglutin AIHA, although this case suggests that warm agglutination is possible. Macrocytic anemia may also worsen AIHA. Further studies are needed to delineate causation. REFERENCE #1: Hill A, Hill QA. Autoimmune hemolytic anemia. Hematology Am Soc Hematol Educ Program. 2018;2018(1):382-389. doi:10.1182/asheducation-2018.1.382 REFERENCE #2: Fadeyi EA, Simmons JH, Jones MR, Palavecino EL, Pomper GJ. Fatal autoimmune hemolytic anemia due to immunoglobulin g autoantibody exacerbated by epstein-barr virus. Lab Med. 2015 Winter;46(1):55-9. doi: 10.1309/LM9OWRF64OGQODEA. PMID: 25617394. REFERENCE #3: Vucelic V, Stancic V, Ledinsky M, Getaldic B, Sovic D, Dodig J, Grbac L, Gacina P, Rincic G, Carzavec D. Combined megaloblastic and immunohemolytic anemia associated--a case report. Acta Clin Croat. 2008 Dec;47(4):239-43. PMID: 19388472. DISCLOSURES: No relevant relationships by Mateus Fernandes, source=Web Response

Hemolytic anemia and plasma exchange

Hemolytic anemia is a disease caused by autoantibodies and resulting in various complaints and clinical symptoms. In about half of cases, the cause of autoimmune hemolytic anemia can not be determined. Corticosteroids are the first-line treatment option for warm autoantibody-related hemolytic anemia. In patients who develop steroid side effects or do not respond adequately, other immunosuppressives may be preferred. In case a rapid response is required or fulminant hemolysis occur, human immunoglobulins (IVIGs) may be added to treatment. Finally, plasma exchange (PE) may additionally be utilised. The essence of PE is based on the removal of immune complexes, protein-bound toxins, autoantibodies and high molecular weight solutes and protein-bound solutes. The main clinical aim of the removal of solutes is usually to gain a faster response than immunosuppressive therapy. Studies related to hemolytic anemia and PE are usually based on case reports. Our case report is about a patient with severe IgG subtype hemolytic anemia. The treatment was started with 1 mg/kg methylprednisolone; to which there was no response with weekly rituximab 375 mg/m2 and IVIG administered. Because of unresponsiveness to all of the immunosuppresives, a total of 5 sessions of PE were added to the treatment procedure every other day. After these sessions, the requirement for transfusions has decreased and the patient underwent splenectomy. The patient is currently being followed up only on oral cyclosporine and the last hemoglobin level was 14.7 g /dl. In severe and refractory anemia, especially in the case of cardiovascular imbalance in fulminant hemolysis, PE may be preferred as a third series option after immunosuppressive treatments and play a role as a bridge to splenectomy.

Aautoimmune Hemolytic Anemia: Pattern of Clinical Presentation and Management Outcome — a Nine Year Observation from a Tertiary Care Hospital in Saudi Arabia

Introduction: Autoimmune hemolytic anemia (AIHA) is characterized by production of auto-antibodies that bind to antigen on the erythrocyte surface that leads to its premature destruction and removal from the circulation by macrophages. Occurrence of AIHA in children and adolescents is rare, exact incidence unknown. Objective of this retrospective study was to assess clinical and laboratory characteristics, and management outcome of patients diagnosed with AIHA seen at Pediatric Hematology/Oncology department of King Faisal specialist Hospital and Research Center ,Riyadh from 2005 to 2014. Method: Retrospective chart review of patients (1-14 yrs.) diagnosed with AIHA was conducted. Children were excluded if they have congenital hemolytic anemia, such as hemoglobinopathies, congenital membranopathy and erythrocyte enzyme deficiencies. Result: Thirty-one patients identified, 19(61%) female and 12(39%) male with a median age at diagnosis of 6 years (0.1-12.4). The direct Coombs test was positive in 23 (74%) patients. Underlying diseases observed as cause of AIHA in 14 (45%) patients: majority secondary to viral infections followed by severe combined immunodeficiency syndrome post bone marrow transplant GVHD complication, while systemic lupus erythematosus, antiphospholipid antibody syndrome, autoimmune hepatitis, hypereosinophilic syndrome, Hyper IgE syndrome, post-liver transplant, diabetes was observed in individual cases. Remaining 17 (55%) patients diagnosed as primary AIHA .Corticosteroids and/or immunoglobulin was given as first line of treatment to 64.5% (20) patients while 35.5% (11) required Rituximab and/or splenectomy as second line of treatment, of which 73%(8) were diagnosed as primary AIHA. Five-year overall survival (Kaplan-Meir) rate of 89% was observed with twenty-seven alive patients showing partial or complete response ,while four patients died due to underlying diseases.Conclusion: Our results demonstrates patients responding to first line of treatment, however serious cases required management through second line of treatment. Further, a regional multicenter observational study will enable better understanding of differences in disease presentation and treatment outcomes. DisclosuresNo relevant conflicts of interest to declare.

PSY25 FACTORS BEHIND AUTOIMMUNE HEMOLYTIC ANEMIA

The mechanism of autoimmune hemolytic anemia (AIHA) is the production of antibodies by the body against its own red blood cells. In most cases, the cause of AIHA cannot be determined (idiopathic autoimmune hemolytic anemia), and it’s frequently associated with other diseases, or caused by certain substances get into the human body.

Causes of autoimmune hemolytic anemia and its clinical presentation.

Objectives: To evaluate various causes of autoimmune hemolytic anemia and its presenting signs and symptoms. Study Design: Cross sectional study. Setting: Fatima Jinnah Medical College Lahore. Period: November 2018 to April 2019. Material &amp; Methods: In this study 90 cases were included having age range of 14-75 years with mean age of 46.5 year with the possibility of autoimmune hemolytic anemia (AIHA). Screening test used for evaluating AIHAin this study include Direct and Indirect Antiglobulin Tests and Cold Agglutinin Titer (CAT). All relevant data was documented properly. Results: Total 90 cases were included in the study comprising on 71% female and 29% male cases. 22.2% cases were having primary and 77.8% were having secondary autoimmune hemolytic anemia. Most common presenting complaint was generalized body weakness in 25(27.7%) cases and on examination most common finding was splenomegaly in 30(33.3%) cases. Hemoglobin was less than 8g/dl in 28(31%) cases. Direct Antiglobulin test was positive in 64(71%) cases, DAT and IATboth were found to be positive in 22(24.4%) cases and DAT and CAT both found positive in 4(4.4%) cases. Blood transfusion was done in 28% cases having severe anemia. Most common cause of autoimmune hemolytic anemia found among study group patients was connective tissue disorder in 25(27.8%) cases. P-value less than 0.05 were considered significant and more than 0.05 was non-significant. Conclusion: In our study autoimmune hemolytic anemia was mostly found in female population with most common presentation of generalized body weakness, pallor of hands, hepatosplenomegaly and severe anemia. Most common cause found of AIHA was connective tissue disorders.

Autoimmune hemolytic anemia- an initial presentation in childhood systemic lupus erythematosus

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that can involve any organ system. It predominantly affects women aged 20 to 40 years. In 10% to 15% of patients, the diagnosis is first established during childhood. Childhood SLE is greater in severity, abrupt with atypical presentation at onset. A 12-year-old girl presented with fever of 8 days and vomiting of 2 days duration. On examination there was pallor and hepatospleenomegaly. Hematologic investigations showed picture of hemolytic anemia. RBCs showed auto-agglutination. Suspecting autoimmune hemolytic anemia, Direct Coombs test was done and was positive. Patient later developed malar rash and hematuria. Suspecting the cause of autoimmune hemolytic anemia to be SLE, Antinuclear antibody, Anti double stranded DNA antibody, Anti Smith antibody were done and showed positive result. Hence the diagnosis was confirmed to be Autoimmune Hemolytic Anemia Due to Systemic Lupus Erythematosus.

Autoimmune hemolytic anemia and ovarian dermoid cysts in pregnancy

Ovarian teratoma is a rare cause of autoimmune hemolytic anemia (AIHA) by warm antibodies, resistant to corticosteroid therapy. This also implies that ovarian teratoma should be included in the differential diagnosis of AIHA, whether or not associated with pregnancy. We present a case of a primigravida who presented with ovarian dermoid cysts and AIHA at 24 weeks of gestation. The patient received corticosteroids, intravenous immunoglobulin, rituximab, and multiple blood transfusions, with no significant improvement. Hemoglobin levels returned to normal only after laparoscopic ovarian cystectomy. Autoimmune hemolytic anemia caused by dermoid cyst is a rare condition especially in pregnancy. However, in light of similar case reports and review of the existing literature, we conclude that surgical excision should be considered when AIHA and ovarian teratoma coexist.

Warm-reactive (immunoglobulin G) autoantibodies and laboratory testing best practices: review of the literature and survey of current practice.

Warm-reactive autoantibodies (WAAs) are the most common cause of autoimmune hemolytic anemia (AIHA) and can also be present without clinically significant hemolysis. WAAs complicate immunohematological testing, yet there is no commonly accepted approach to laboratory evaluation and red blood cell (RBC) selection. We searched PubMed/Cochrane Central for articles that described testing methodology and blood selection for patients with WAAs. We developed a 31-question survey regarding local practice for immunohematology testing and RBC selection in patients with WAAs (with or without AIHA). Eighty-six studies met the inclusion criteria and the aims of this review. Most of the literature was comprised of retrospective studies that often did not correlate laboratory results with clinical findings. Evidence-based protocols to guide testing and RBC selection for transfusion in patients with WAAs are lacking. Individuals representing 54 laboratories completed the survey. The responses indicated that numerous methodologies are used to identify underlying alloantibodies: 75% of respondents use autoadsorption; in patients who have a recent history of transfusion, 76% of respondents use alloadsorption; 58% of respondents perform direct antiglobulin testing (DAT) each time the indirect antiglobulin test is positive; and 48% perform eluate studies at the initial identification of WAAs. Responding laboratories may use phenotyping (98%) or genotyping (80%) at some point in the work-up. Seventy-five percent of respondents provide phenotype-matched or genotype-matched RBCs for transfusion. There is wide variability in immunohematology testing and RBC selection practices for patients who have WAAs (with or without AIHA). Future studies are needed to evaluate and compare the effectiveness of different testing algorithms and transfusion strategies.

AUTOIMMUNE HEMOLYTIC ANEMIA (AIHA)

Objectives: Autoimmune hemolytic anemia (AIHA)- an immunological diseaseresulting from red cell hemolysis caused by circulating autoantibodies against antigens on redcell membrane. Positive direct antiglobulin test (DAT) always exist in association with AIHAand form basis for its serologic diagnosis. The objective of our study was to determine clinicalpresentation and etiological pattern in autoimmune hemolytic anemia at a tertiary care hospital.Study Design: Descriptive, cross-sectional study. Setting: Medical unit I of Liaquat UniversityHospital Jamshoro / Hyderabad. Period: 1st January 2010 to 30th June 2010. Patients andMethods: We enrolled 125 patients of either sex and ages from 13 to 81 years for evaluationof possible AIHA. We screened patients by performing direct and indirect antiglobulin tests(DAT and IAT) and cold agglutinin titre (CAT) levels. Pregnant women or those with historyof blood transfusion in previous three months, DAT positive patients due to Rh and ABOincompatibilities in neonates and IAT positives cases in Rh-negative pregnant women wereexcluded. Results: We evaluated 125 patients who were DAT positive autoimmune hemolyticanemia. About 93(74.4%) were females and 32(25.6%) males with female to male ratio of2.9:1. The mean age of our patients was SD ± 36.73 ± 9.32 years. Our patients commonlypresented, generalized weakness in 33(26.4%), pallor of face and extremities in 22(17.6%)and breathlessness in 20(16%) respectively. On clinical examination, moderate to severeanemia was noted in 100(80%), splenomegaly in 40(32%), hepatosplenomegaly in 28 (22.4%)and no visceromegaly in 30(24%) of our cases. We found 35(28%) with primary and 90(72%)patients due to secondary causes of AIHA. The connective tissue disorders, renal failure andhematological disorders were common causes of secondary AIHA in this study. Conclusion:Our study showed females in their thirties presented with generalized weakness, pallor of faceand extremities and breathlessness. Majority had secondary AIHA due to consecutive tissuedisorders, renal failure and hematological disorders as underlying causes. Doctors must becautious regarding whole blood transfusion as means for treating mild to moderate anemia.

English

Objectives: Autoimmune hemolytic anemia (AIHA)- an immunological diseaseresulting from red cell hemolysis caused by circulating autoantibodies against antigens on redcell membrane. Positive direct antiglobulin test (DAT) always exist in association with AIHAand form basis for its serologic diagnosis. The objective of our study was to determine clinicalpresentation and etiological pattern in autoimmune hemolytic anemia at a tertiary care hospital.Study Design: Descriptive, cross-sectional study. Setting: Medical unit I of Liaquat UniversityHospital Jamshoro / Hyderabad. Period: 1st January 2010 to 30th June 2010. Patients andMethods: We enrolled 125 patients of either sex and ages from 13 to 81 years for evaluationof possible AIHA. We screened patients by performing direct and indirect antiglobulin tests(DAT and IAT) and cold agglutinin titre (CAT) levels. Pregnant women or those with historyof blood transfusion in previous three months, DAT positive patients due to Rh and ABOincompatibilities in neonates and IAT positives cases in Rh-negative pregnant women wereexcluded. Results: We evaluated 125 patients who were DAT positive autoimmune hemolyticanemia. About 93(74.4%) were females and 32(25.6%) males with female to male ratio of2.9:1. The mean age of our patients was SD ± 36.73 ± 9.32 years. Our patients commonlypresented, generalized weakness in 33(26.4%), pallor of face and extremities in 22(17.6%)and breathlessness in 20(16%) respectively. On clinical examination, moderate to severeanemia was noted in 100(80%), splenomegaly in 40(32%), hepatosplenomegaly in 28 (22.4%)and no visceromegaly in 30(24%) of our cases. We found 35(28%) with primary and 90(72%)patients due to secondary causes of AIHA. The connective tissue disorders, renal failure andhematological disorders were common causes of secondary AIHA in this study. Conclusion:Our study showed females in their thirties presented with generalized weakness, pallor of faceand extremities and breathlessness. Majority had secondary AIHA due to consecutive tissuedisorders, renal failure and hematological disorders as underlying causes. Doctors must becautious regarding whole blood transfusion as means for treating mild to moderate anemia.

Cold agglutinin mediated autoimmune hemolytic anemia due to acute cytomegalovirus infection in an immunocompetent adult

Abstract Introduction A case of cold agglutinin syndrome due to cytomegalovirus infection is being reported. Aim To learn rare manifestation of cytomegalovirus (CMV) infection. Case study Though CMV infections are not very rare in immunocompetent individuals, CMV leading to hemolytic anemia is a rare phenomenon. We report a case of cold agglutinin mediated autoimmune hemolytic anemia (AIHA) in one such patient due to CMV infection. He recovered fully without receiving steroids or antiviral therapy. Results and discussion Cold agglutinin mediated AIHA accounts for 7%–25% of all causes of AIHA. The most common infections include Epstein–Barr virus and Mycoplasma pneumoniae . CMV is associated with cold agglutinin mediated hemolytic anemia predominantly in immunosuppressed individuals and children. A number of studies have indicated that CMV infection in the immunocompetent host may be more common than previously thought. It can present itself in many ways but AIHA is rare. We present this case for its rarity. Conclusions CMV may also cause serious manifestations in an immunocompetent patient.

Metalose: Causa Rara de Anemia Hemolítica Autoimune

Hemolytic anemia may be associated with multiple etiologies, including toxic substances, such as metals, which is a rare cause. 55-year-old male, who underwent a total arthroplasty of the right hip (uncemented prostheses with ceramic-ceramic articulation with an acetabular component consisting of a dome composed of an alloy of titanium, aluminum and vanadium into which fitted a ceramic 'insert'). Approximately 4 years after surgery the patient complained of noise originating from the prosthesis which occurred on movement. A surgical revision was performed and showed the presence of dark thick intracapsular fluid, fracture of the ceramic acetabular 'insert' and signs of wear of the acetabular metal dome. Extensive washing was carried out and the fractured ceramic 'insert' was replaced for a polyethylene 'insert'. Two months later he was referred to the Emergency Room due to worsening of his general health, floating in the right hip and mucocutaneous jaundice. Laboratory tests suggested autoimmune hemolytic anemia. Arthrocentesis was performed and a large volume of metal fluid was drained off. The CT scan showed a large heterogeneous pelvic cystic collection seeded with prosthesis fragments, suggestive of metallosis. Hemolytic anemia was explained as toxicity of the particles and metal ions caused by the wear of the prosthesis. The patient was started on a high-dose steroid treatment. Afterwards, when he was stable, prosthesis components replacement and drainage of pelvic debris fluid were carried out. After the fracture of the ceramic 'insert' the ceramic head began to articulate directly with the metallic acetabular component, causing noise and wear with release of particles and ions. This caused a cystic pelvic abscess, which went unnoticed on the first surgical revision. Surgical debridement lead to the cystic collection extending into the adjacent tissues and the systemic circulation, triggering serious systemic effects, such as autoimmune hemolytic anemia. The potential toxicity of each of the metal elements of this prosthesis is unknown, and there are still no available laboratory tests for its detection. Metallosis is a rare cause of autoimmune hemolytic anemia.

Surface localization of high-mobility group nucleosome-binding protein 2 on leukemic B cells from patients with chronic lymphocytic leukemia is related to secondary autoimmune hemolytic anemia

Chronic lymphocytic leukemia (CLL) is the main cause of autoimmune hemolytic anemia (AHA). However, the cellular basis underlying this strong association remains unclear. We previously demonstrated that leukemic B cells from patients with CLL recognize the erythrocyte protein Band 3, a prevalent autoantigen in AHA. Here we show that the major binding site of Band 3 on leukemic cells is an extrinsic protein identified as high-mobility group nucleosome binding protein 2 (HMGN2), a nucleosome-interacting factor which has not been previously reported at the cell surface. T lymphocytes do not express HMGN2 or bind Band 3. Removal of HMGN2 from the cell membrane abrogated the capacity of Band 3-pulsed CLL cells to induce CD4 + T cell proliferation. We conclude that surface HMGN2 in leukemic B cells is involved in Band 3 binding, uptake and presentation to CD4 + T lymphocytes, and as such may favor the initiation of AHA secondary to CLL.

Clinical Characteristics and Long Term Outcomes of Warm Type Autoimmune Hemolytic Anemia

Back groundWarm type autoimmune hemolytic anemia (AIHA) is the disease which antibody reacts with self-antigen on red blood cell. Due to the uncommon of this disease, there is a little data about long term outcomes and response to therapy especially second line treatment.MethodsThis is a retrospective single center study from 2002 to 2013. The diagnosis of AIHA was made by positive direct Coombs’ test with clinical hemolysis and confirmed by Hematologist. Clinical data and long term outcome were reviewed and analyzed.ResultsDuring that period, 101 patients were reviewed, 77% were female, median age was 43 (15-83) years. The median hemoglobin level at diagnosis was 5.4 (2-10) g/dl. Primary AIHA was found in 61%. The secondary causes were SLE (64%), solid malignancy (13%), lymphoma (10%), drug (8%) and infection (5%). The secondary cause from SLE was commonly found in female (96%) (P<0.001). There was the difference of age between secondary cause from SLE (<50 years) and malignancy (>50 years) (p=0.013). These results showed the interesting data that secondary cause of AIHA needed to be searching especially SLE in young female and secondary cancer in elderly patients. Not only cause could be identified but also the specific treatment needed to be given according to secondary cause.Interestingly, most patients (96%) were initially response to steroid which was not different between primary and secondary AIHA. Second line treatments were required in 33 patients (33%). The indications were steroid dependent (58%), relapse (30%) and others (12%). The second line treatments were including cyclophosphamide (52%), azathioprine (21%), cyclosporine (6%), splenectomy (6%), danazol (6%) and others (9%). The overall response rate for second line was 93%. SLE group received second line therapy more than non SLE group (p<0.001). In the light of data from this study showed that this disease had a good prognosis in both frontline steroid and second line treatment. Relapse was occurred in 50 patients (50%). Most relapse occurred > 3 years after diagnosis (58%) and more common in SLE group (p<0.001). These findings illustrated the importance nature of the disease that need long follow up due to high relapse rate around half of patients.At the median follow up 53 months, the overall survival (OS) and event free survival (relapse and death) were 84% and 48%, respectively. The independent factor for decreasing OS was age >50 years with HR 3.09 (95% CI 1.09-8.73, p=0.03) and malignancy with HR 4.06 (95% CI 1.18-13.97, p=0.03). The only significant factor for relapse is age >50 years with HR 2.08 (95% CI 1.21-3.57, p = 0.008). Twenty patients were death. The common cause of death was sepsis (30%) due to heavily immunosuppressive treatment.ConclusionAIHA has good prognosis and long term survival especially in young patient without secondary malignancy. The search for secondary cause especially malignancy is important. Most patients have responded initially to steroid and high response rate to second line therapy. The most common cause of death was sepsis which related to treatment side effect. Carefully adjust and rapid taper immunosuppressant is considerable to avoid serious complication. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Treatment of autoimmune hemolytic anemia at the departement of hematology of the UMC Ljubljana in the period from 2000–2011

Background: Autoimmune hemolytic anemia (AIHA) is an acquired hemolytic anemia and can be treated as an idiopathic or primary disease or can be associated with some other hematologic diseases (secondary). AIHA is a disease characterized by the presence of auto-antibodies directed against antigens on the red cell membrane, rare can the result of Coombs test be negative although there are all signs of AIHA present. Depending on the temperature at which auto-antibodies bind to the surface of an erythrocyte, we talk about AIHA with warm agglutinins and AIHA with cold agglutinins. Treatment is diverse as are also the causes of AIHA. The most important thing is to decrease the production of antibodies or to prevent the erythrocyte from decomposing with bound antibodies and to treat the disease symptomatically. Patients and methodes: With a retrospective analysis we searched through database of 70 patients with idiopathic (90 %) and secondary (10 %) autoimmune hemolytic anemia with warm (84.3 %) and cold (10 %) type agglutinin, who were treated at the Hematologic Department of the UMC Ljubljana during the period from 2000–2011. I processed the data with the SPSS program system. Results: Methylprednisolone was the first choice of treatment in 92. 5 % patients with primary and secondary AIHA with response rate of 79 % and 70.9 % complete remission rate. 22.7 % of the patients with complete remission after corticosteroids treatment , relapsed during the period of time and received a second-line treatment with cyclosporine (87 % response rate), rituximab or underwent splenectomy. Another attempt was made with methylprednisolone. The patients, who were refractory to the initial methylprednisolone treatment or required a higher maintenance dose, were treated in second line with cyclosporine (69 % response rate), rituximab (57 % responsee rate). One patient was treated successfully with mycophenolate mofetil and two patients, who were refractory to all other treatments, achieved a stable state of disease with splenectomy. The effective treatment for patients with cold agglutinin AIHA were corticosteroids and rituximab. We achieved an improvement of the condition in secondary AIHA when we treated the underlying disease. 6 % of all patients were refractory to any kind of treatment. Conclusions: Treatment with glucocorticoids is the most efficient treatment for patients with AIHA with warm and cold agglutinin. If the patients are refractory to the first-line therapy, we switch to a second-line therapy, which depends on etiology and concomitant diseases. Patients who are resistant to standard available treatments generally present with severe complications.

Autoimmune Hemolytic Anemia in Treatment-Naïve Chronic Hepatitis C Infection

Purpose: Hepatitis C Virus (HCV) is a blood borne pathogen that infects the liver and is associated with great morbidity. Chronic HCV infection can lead to cirrhosis, hepatocellular carcinoma, and ultimately liver failure. Less commonly known extrahepatic manifestations of HCV exist as numerous studies have been published demonstrating Autoimmune Hemolytic Anemia (AIHA) in chronic Hepatitis C patients receiving Ribavarin or Interferon. On the contrary, there is minimal literature demonstrating AIHA in treatment-naive chronic hepatitis. Case Presentation: A 53-year-old man with chronic Hepatitis C infection presented with 7 days of sharp right upper quadrant abdominal pain complicated by rapidly increasing abdominal girth, nausea, vomiting, weakness, fever and jaundice. His HCV course was complicated by cirrhosis, esophageal varices, portal hypertensive gastropathy and spontaneous bacterial peritonitis. Physical examination: Jaundiced sleepy male with normal vital signs. Scleral icterus, distended abdomen tender to palpation in the right upper quadrant, gynecomastia, diffuse spider angiomata on anterior chest, and +2 bilateral pitting edema up to the knees. No asterixis, palmar erythema, or caput medusae. Laboratory data: WBC 5700/UL, Hemoglobin 8.3 g/dl, MCV 112.4, platelets 47,000/UL. Indirect bilirubin of 14.3 mg/dl was worrisome for hemolytic anemia. Reticulocyte count 9.6% and direct Coomb's test antibody positive. Peripheral smear showed increased spherocytes, polychromasia, and thrombocytopenia consistent with AIHA. Workup: Etiologies of AIHA include malignancy, SLE, Ribavarin and Interferon. MRI and CT abdomen with contrast illustrated cirrhosis, but did not depict neoplastic lesions or lymphadenopathy. Chest CT and x-ray demonstrated no neoplasms, mediastinal or axillary lymphadenopathy, and no changes of the bony thorax consistent with a cancerous process. Bone marrow biopsy demonstrated erythroid hyperplasia with cell lines. No tumor or lymphoma was noted. Thus, malignancy was ruled out as an etiology of AIHA. SLE was subsequently ruled out with a negative ANA panel, and iatrogenic etiology was non-contributory as the patient had never received Ribavarin or Interferon. Conclusion: We present a rare case of AIHA infection where conceivably all etiologies of AIHA were thoroughly ruled out - demonstrating HCV as a unique and novel cause of AIHA. This is of great interest in idiopathic AIHA, as physicians we can look to HCV as an underlying source of AIHA. More recently, HCV is becoming an epidemic in the United States. Thus, unprecedented medical conditions associated with HCV are of great interest.